Search bioRxiv⌕ Search

Biology subjects

Ethridge, L.

Publications and source records attributed to Ethridge, L..

4 recordsLinked to original sources

Aberrant Neural Entrainment to Word-Level Speech Patterns in Fragile X Syndrome: Evidence for a Statistical Learning Deficit

Fragile X syndrome (FXS), the most common inherited cause of intellectual disability and autism spectrum disorder, causes significant language and cognitive impairments. Statistical learning refers to the ability to extract patterns from sensory input through mere exposure and plays a central role in language acquisition. Surprisingly, statistical learning in FXS has not been explored. Given that children with FXS typically follow a delayed developmental trajectory for language, we hypothesized that they would show impaired statistical learning. To test this hypothesis, we used an EEG measure of neural entrainment to index statistical learning of hidden trisyllabic words within a continuous speech stream in children with FXS (n = 17) and in typically developing controls (n = 31). Children with FXS showed significantly reduced neural entrainment to words compared to controls, particularly in the superior temporal gyrus and transverse temporal gyrus (primary auditory cortex), providing evidence of statistical learning impairment. Notably, syllable-level entrainment was preserved or even enhanced in FXS, indicating that word-level deficits cannot be attributed to general auditory processing impairments. In addition, while typically developing controls showed an increase in word-level entrainment over the course of learning, children with FXS failed to show a similar increase over time. Taken together, this pattern of results demonstrates that children with FXS can process rapid, lower-order acoustic structure but struggle to integrate these syllables into longer, chunk-like word representations. Overall, these findings suggest that statistical learning is impaired in FXS, and also suggest neural entrainment to statistical structure as a potential therapeutic target.

neuroscience↗

Event-Related Spatio-Spectral Perturbation (ERSSP): A Scalp-Wide EEG Analysis Framework for Capturing Extralemniscal Thalamocortical Activity, Validated Using a Fragile X Syndrome Model

The extralemniscal thalamocortical pathway regulates large-scale modulation of cortical states but remains inaccessible to traditional EEG analysis due to its diffuse, variable, and asynchronous nature. To address this, we introduce the Event-Related Spatio-Spectral Perturbation (ERSSP) framework, which quantifies spatially distributed time-frequency responses. ERSSP summarizes the number of channels exhibiting significant spectral perturbations, capturing diffuse cortical dynamics from sensor-space EEG. We validated this approach using a passive auditory habituation task in individuals with Fragile X Syndrome (FXS), a condition marked by disrupted thalamocortical modulation. ERSSP revealed enhanced spatial extent of power increases (but not phase-locking) in FXS compared to controls. Results also showed expected gender differences, further supporting biological sensitivity of ERSSP. ERSSP provides a conceptually simple and computationally efficient method for quantifying broadly distributed sensory modulation and may enable new insights into thalamocortical function in both basic and clinical neuroscience.

neuroscience↗

A human electrophysiological biomarker of Fragile X Syndrome is shared in V1 of Fmr1 KO mice and caused by loss of FMRP in cortical excitatory neurons

Predicting clinical therapeutic outcomes from preclinical animal studies remains an obstacle to developing treatments for neuropsychiatric disorders. Electrophysiological biomarkers analyzed consistently across species could bridge this divide. In humans, alpha oscillations in the resting state electroencephalogram (rsEEG) are altered in many disorders, but these disruptions have not yet been characterized in animal models. Here, we employ a uniform analytical method to show in males with fragile X syndrome (FXS) that the slowed alpha oscillations observed in adults are also present in children and in visual cortex of adult and juvenile Fmr1-/y mice. We find that alpha-like oscillations in mice reflect the differential activity of two classes of inhibitory interneurons, but the phenotype is caused by deletion of Fmr1 specifically in cortical excitatory neurons. These results provide a framework for studying alpha oscillation disruptions across species, advance understanding of a critical rsEEG signature in the human brain and inform the cellular basis for a putative biomarker of FXS.

neuroscience↗

Frontal Cortex Hyperactivation and Gamma Desynchrony in Fragile X Syndrome: Correlates of Auditory Hypersensitivity

Fragile X syndrome (FXS) is an X-linked disorder that often leads to intellectual disability, anxiety, and sensory hypersensitivity. While sound sensitivity (hyperacusis) is a distressing symptom in FXS, its neural basis is not well understood. It is postulated that hyperacusis may stem from temporal lobe hyperexcitability or dysregulation in top-down modulation. Studying the neural mechanisms underlying sound sensitivity in FXS using scalp electroencephalography (EEG) is challenging because the temporal and frontal regions have overlapping neural projections that are difficult to differentiate. To overcome this challenge, we conducted EEG source analysis on a group of 36 individuals with FXS and 39 matched healthy controls. Our goal was to characterize the spatial and temporal properties of the response to an auditory chirp stimulus. Our results showed that males with FXS exhibit excessive activation in the frontal cortex in response to the stimulus onset, which may reflect changes in top-down modulation of auditory processing. Additionally, during the chirp stimulus, individuals with FXS demonstrated a reduction in typical gamma phase synchrony, along with an increase in asynchronous gamma power, across multiple regions, most strongly in temporal cortex. Consistent with these findings, we observed a decrease in the signal-to-noise ratio, estimated by the ratio of synchronous to asynchronous gamma activity, in individuals with FXS. Furthermore, this ratio was highly correlated with performance in an auditory attention task. Compared to controls, males with FXS demonstrated elevated bidirectional frontotemporal information flow at chirp onset. The evidence indicates that both temporal lobe hyperexcitability and disruptions in top-down regulation play a role in auditory sensitivity disturbances in FXS. These findings have the potential to guide the development of therapeutic targets and back-translation strategies.

neuroscience↗